Fly Stem Cells on Diet

"In starved flies there are fewer
stem cells and they divide slower,"
says Wang. "However, a small pool
of active stem cells remained even
after prolonged starvation."

A study led by Salk assistant professor Leanne Jones
revealed that stem cells can sense a decrease in available nutrients
and respond by retaining only a small pool of active stem cells for tissue
maintenance. When, or if, favorable conditions return, stem cell numbers
multiply to accommodate increased demands on the tissue, her team
reported in the journal Current Biology.

Elucidating the mechanisms by which hormonal signaling influences
stem cell behavior under normal conditions and in response to stress
provides important insights into the activities of stem cells in regenerative
medicine, during wound repair, and in individuals experiencing
metabolic stress.

"Tissues that are maintained by stem cells respond to adverse environmental
conditions by reducing the overall number of stem cells, as well
as the activity of those stem cells, but maintain them in such a state that
they can respond quickly and effectively once the nutritional conditions
become more favorable," says Jones.

Stem cells, with their defining characteristics—extensive proliferative
potential and an ability to give rise to one or more specialized cell types—are common in early embryos. But by adulthood, only a few stem cells
remain, tucked away in their own private niches. They have, nonetheless,
retained a remarkable capability: they can operate at a "steady state"
to maintain and repair tissues.

When food becomes scarce, animals may go through a period of
reduced metabolism to allocate limited resources and maintain tissue
homeostasis. In addition, a number of animals, such as those that
hibernate, experience a decrease in metabolic rate as part of their
normal cycle.

"But very little was known about the effect of chronic changes in
metabolism on adult stem cells and the tissues that they maintain,"
says Jones.

To learn more, the researchers addressed the effects of nutrient
availability by feeding their flies a "poor," proteinless diet for several
weeks. As a result, the levels of circulating insulin-like peptides
plummeted and the number of stem cells in the flies' testes and intestines
started to decline. Upon re-feeding, insulin-like peptide expression and
stem cell count recovered quickly.

Jones and her team think it likely that the link between hormonal
signaling and stem cell response will turn out to be important not only
for nutrient deprivation but also for other situations where a body's
metabolism might be altered.

"One may think of how tissue homeostasis is modified in a situation
when the body cannot accurately monitor or utilize available nutrients—
for instance, in the case of a person who is diabetic," says Jones.

"Further investigating the relationship between nutrient availability
and stem cell behavior may also lead to clues for why people who are
overfed or malnourished are prone to develop metabolic diseases or cancers, in which cells fail to differentiate properly," adds
postdoctoral researcher and co-first author Lei Wang, Ph.D.

An intriguing question arising from the study is whether an
extreme shift in a patient's eating habits could be considered an
element of a treatment.